Expression of rearranged TCRγ genes in natural killer cells suggests a minor thymus-dependent pathway of lineage commitment

Veinotte, Linnea Lora; Greenwood, Chelsea Pamela; Mohammadi, Nastaran Keshavarz; Parachoniak, Christine A.; Takei, Fumio

doi:10.1182/blood-2005-07-2797

Cited by 48 publications

(59 citation statements)

References 37 publications

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“…Considerable work has been done to show that NK cells may rely on V(D)J recombination activity early in their development (44)(45)(46)(47). Using a GFP-type marking system, Pilbeam et al were able to permanently mark NK cells that performed recombination in their developmental history (47).…”

Section: Discussionmentioning

confidence: 99%

CD1d-unrestricted NKT cells are endowed with a hybrid function far superior than that of iNKT cells

Farr¹,

Choi³

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Significance The Immunological Genome Project Consortium has recently identified a gene-expression program that links invariant natural killer T (iNKT) cells to NK cells. While this is true, our study provides molecular and functional evidence demonstrating that CD1d-independent NKT cells are uniquely programmed with a hybrid function far superior to that of iNKT cells. Such a unique feature enables this subset of NKT cells to contribute to adaptive immunity (like T cells) and at the same time act as a prominent player in innate defense (like NK cells).

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Section: Discussionmentioning

confidence: 99%

CD1d-unrestricted NKT cells are endowed with a hybrid function far superior than that of iNKT cells

Farr¹,

Choi³

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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“…Studies of the intraepithelial lymphocytes isolated from the small intestine of patients with celiac disease have uncovered oligoclonal populations of ab-TCR + CD8 + T cells displaying lower amounts of TCR/CD3 on the cell surface and an abundance of "NK receptors", suggesting that these cells have been "re- programmed" to acquire receptors enabling them to mediate functions usually mediated by NK cells [13]. Recent studies have also described a minor population of NK1.1 + cells lacking cells surface expression of CD3 in the thymus and spleen of wild-type and TCRb -/-d -/-mice that express in-frame rearranged TCRc genes [14]. These cells are absent in nude mice, implying a requirement for the thymus for their development.…”

Section: Expression Of "Nk Receptors" On T Cellsmentioning

confidence: 99%

Back to the future –defining NK cells and T cells

Lanier

2007

Eur J Immunol

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In this issue of the European Journal of Immunology (EJI), Stewart et al. report about a population of cd-T cells expressing an extensive repertoire of NK cell receptors, and the presence of non-rearranged germline TCRd transcripts in conventional NK cells. These findings and other recent studies highlight the similarities of NK cells and T cells and the problems in discriminating between these two lineages.

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“…Therefore, CD127 expression is not sufficient to unambiguously identify a single population of NK-gated cells. Whilst early thymic progenitors can differentiate into NK cells [41], evidence for its occurrence in wildtype mice, which relies on the use of "thymic" NK markers not found in athymic mice, including CD127 [38] and TCR gene rearrangements [42], must consider the similarity of NK-like cd T cells to bona fide NK cells. Following surface staining, intracellular staining of CD3e was performed using the same CD3e mAb conjugated to a different fluorochrome.…”

mentioning

confidence: 99%

Germ‐line and rearranged Tcrd transcription distinguish bona fide NK cells and NK‐like γδ T cells

et al. 2007

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NK cells and cd T cells are distinct subsets of lymphocytes that contextually share multiple phenotypic and functional characteristics. However, the acquisition and the extent of these similarities remain poorly understood. Here, using T cell receptor d locus-histone 2B-enhanced GFP (Tcrd-H2BEGFP) reporter mice, we show that germline transcription of Tcrd occurs in all maturing NK cells. We also describe a population of mouse NK-like cells that are indistinguishable from "bona fide" NK cells using standard protocols. Requirements for V(D)J recombination and a functional thymus, along with very low-level expression of surface TCRcd but high intracellular CD3, define these cells as cd T cells. "NK-like cd T cells" are CD127 + , have a memory-activated phenotype, express multiple NK cell receptors and readily produce interferon-c in response to IL-12/IL-18 stimulation. The close phenotypic resemblance between NK cells and NK-like cd T cells is a source of experimental ambiguity in studies bridging NK and T cell biology, such as those on thymic NK cell development. Instead, it ascribes chronic TCRcd engagement as a means of acquiring NK-like function. IntroductionClassification of NK cells and some cd T cell subsets as innate immune cells is argued by their recognition and response to self ligands and microbial molecules without any requirement for prior specific immunization [1][2][3][4][5]. NK cells are mediators of immunity against various infectious diseases and tumor cells, performing direct cell-mediated cytotoxicity and producing cytokines in response to cell-associated and soluble stimuli [6,7]. They additionally shape adaptive immune responses, mainly through the production of cytokines [8]. Their activation is regulated through germ-line-encoded receptors including NKG2D, the natural cytotoxicity receptors and inhibitory receptors for MHC class I, many of which recognize self-encoded ligands [9][10][11]. Most cd T cell subsets are unconventional T cells that -similar to CD1d-restricted Va14i NKT cells, MR1-restricted MAIT cells and certain populations of CD8 + T cells -are not restricted to classical MHC class I-or MHC class II-bearing specific peptides [2,3]. They have heterogeneous effector functions associated with differential TCRcd usage. Roles have been described in immunity against infectious pathogens and tumors [12] and cd T cells have been strongly implicated in immunosuppressive regulation of the immune system and in the process of wound healing [13,14]. Using TCR transfer experiments, or direct ligand binding, TCRcd ligands have been described for a small number of subsets [5]. In the mouse, cd T cell subsets recognize the non-classical MHC class I molecules T10/T22 [15], and an unknown ligand expressed by keratinocytes [16]. In humans, some Vd1 cd T cells recognize non-classical MHC class I molecules MICA and MICB, and Vc9Vd2 cd T cells have been reported to recognize self and bacterial phosphoantigens, and a complex formed between F1-ATP synthase and apolipoprotein A-1 [5,[17][18][19][20].Du...

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Expression of rearranged TCRγ genes in natural killer cells suggests a minor thymus-dependent pathway of lineage commitment

Cited by 48 publications

References 37 publications

CD1d-unrestricted NKT cells are endowed with a hybrid function far superior than that of iNKT cells

CD1d-unrestricted NKT cells are endowed with a hybrid function far superior than that of iNKT cells

Back to the future –defining NK cells and T cells

Germ‐line and rearranged Tcrd transcription distinguish bona fide NK cells and NK‐like γδ T cells

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